To date, caloric restriction has shown itself to be the most reproducible and promising intervention to improve cancer outcomes in laboratory animals. An intense and expanding area of research is focused on discovering easily achievable interventions that can have long-lasting positive effects. This proposal will explore maternal exercise during pregnancy as a potential short-term intervention that can provide a lifetime of benefits for the next generation. In a small pilot study in mice, offspring born to exercised dams had improved glucose regulation and enhanced stress protection compared to offspring born to sedentary dams. These preliminary findings contribute to the hypothesis that maternal exercise during pregnancy and nursing protects mature offspring against chemical carcinogens because of increased activities of antioxidant enzymes. The first aim is designed to test whether maternal exercise during pregnancy is a realistic intervention that can protect mature offspring from chemical carcinogens. The second aim will look to elucidate the role of the stress-induced transcription factor, nuclear factor erythroid-2 related factor 2, as a potential mechanism for long-lasting protection by perinatal exercise. These studies will provide important information on the potential positive impact maternal exercise may have on offspring cancer protection.